PC-12 cells contain a cytosolic cAMP-dependent protein kinase that phosphorylates two endorgenous substrates as well as histone. Forskolin mimics the effect of cAMP as shown by autoradiography of the substrates. Depolarization of the cells with 150 mM K+ has no effect on basal protein phosphorylation. The addition of CA++ causes a decrease from the basal level of phosphorylation in all bands. The addition of calmodulin and CA++ restores the level of phosphate incorporation in the bands below 90, 000 MW. Nerve growth factor (NGF) induces differentiation of these cells. Cyclic AMP, but not forskolin causes increased phosphorylation.